XELOX Combined With Cadonilimab Versus XELOX as Neoadjuvant Treatment for Locally Advanced, pMMR Rectal Cancer

• Cadonilimab (Drug): 10mg/kg iv on day 1, every 21 day
• Oxaliplatin (Drug): 130mg/m2 iv on day 1, every 21 day
• Capecitabine (Drug): 1000mg/m2 po bid on day 1 to 14, every 21 day

Primary outcomes

• pCR [3 years]: the rate of pathological complete response

Secondary outcomes

• MPR [3 years]: the rate of major pathological response according to Becker-TRG
• DFS [From date of initiation of treatment to date of progression or death due to any cause, whichever occurs first, assessed up to 3 years]: disease free survival
• OS [From date of initiation of treatment to date of death, assessed up to 3 years]: overall survival

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

* Histologically or pathologically confirmed rectal adenocarcinoma located within 5 to 15cm from the anus with a stage of T3-4a or N+ according to the CT or endoscope
* Mesorectal fascia uninvolved
* Sign the informed consent form
* 18 years and older
* Mismatch repair proficient determined by immunohistochemistry
* No prior treatment
* Performance status: ECOG 0-1
* Good organ function:

Blood routine: hemoglobin ≥90g/L, neutrophil ≥1.5×10\^9/L, platelet ≥100×10\^9/L; Renal function: creatinine≤1.5×upper limit of normal (UNL) or creatinine clearance ≥50ml/min; Liver function: total bilirubin (TBIL)≤1.5×upper limit of normal (UNL); ALT≤2.5×UNL, AST≤2.5×UNL; Ejection fraction at least 50% (or lower limit of normal) by echocardiogram

Exclusion Criteria:

* Other pathological category, such as squamous cancer
* Distant metastasis or peritoneum implantation
* Have received chemotherapy or radiotherapy in the past
* Known to have allergic reactions to any ingredients or excipients of experimental drugs
* Unable to swallow or under other circumstance which would drug absorption
* Other active malignant tumors, excluding those who have been disease free for more than 5 years or in situ cancer considered to have been cured by adequate treatment
* Have received colorectal cancer surgery
* Diabetes was not controlled, defined as HbA1c > 7.5% after anti-diabetic drugs or hypertension was not controlled, defined as systolic / diastolic blood pressure > 140 / 90 mmHg after antihypertensive drug
* Myocardial infarction, severe/unstable angina, New York Heart Association (NYHA) class III or IV congestive heart failure in the past 12 months
* Known to be infected with human immunodeficiency virus (HIV), have acquired immunodeficiency syndrome (AIDS) related diseases, have active hepatitis B or hepatitis C
* Pregnant or nursing
* May increase the risk associated with participation in the study or administration of the study drug or mental illness that may interfere with the interpretation of research results
* There are other serious diseases that the researchers believe patients cannot be included in the study